Rub your hands and improve memory – fantasy or reality?

Rub your hands and improve memory – fantasy or reality?

A team of Yonsei biotechnologists and neuroscientists suggests that triboelectricity can be used to convert somatic cells to neurons

Strokes, brain tumors, and neurodegenerative diseases such as multiple sclerosis, Alzheimer’s disease, and Parkinson’s disease, irreversibly destroy neurons in the brain, condemning people to permanent incapacitation or death. Neuronal degeneration is also the primary cause of memory loss and cognitive decline in elderly people. Therefore, neuroscientists have been working on strategies to restore the neuronal population in the brain, which is decreased by aging or disease. Among them, the conversion of pluripotent stem cells to neurons shows promise, but there are ethical issues associated with the use of human embryos. Another approach is direct reprogramming of somatic cells into neurons through transfer of neuron-specific genes; however, one of the major problems is gene delivery, as viral vectors are efficient but unsafe, while non-viral methods using naked DNA, although safe, have low efficiency.

These challenges were addressed by scientists from Yonsei University led by Professor Seung-Woo Cho, who have developed a novel approach to stimulate conversion of somatic cells into neurons using triboelectricity.

How does it work?
The technology is based on the triboelectric effect, a phenomenon that each of us encounters in everyday life when we can feel, hear, and even see sparks (electrical charges) produced by contact or friction between dissimilar materials, such as hair and comb, skin and polyester clothes, etc. The effect has been known from ancient times as “tribo” means “rub” in Greek; however, it began to be exploited only recently, when nanotechnologists created triboelectric generators – devices that can harvest the ambient mechanical energy produced by such trivial activities as, for example, walking or rubbing hands, and convert it to electricity.

In their study, Professor Seung-Woo Cho, Professor Taeyoon Lee, and their colleagues transfected fibroblasts with genes encoding neuron-specific transcription factors using non-viral methods such as electroporation and biodegradable polymeric nanoparticles and subjected them to triboelectric stimulation. Triboelectricity was obtained by periodic press and release of two parallel plates made, respectively, of aluminum (Al) and polydimethylsiloxane (PDMS), materials that demonstrate the maximal degree of static charge polarity and, thus, can generate the strongest current. Surface friction between the plates produced triboelectric charges and current between the two electrodes connected to the cell culture substrate made of highly conductive material (Figure). As a result, cultured fibroblasts were exposed to biphasic triboelectric current, which substantially accelerated their differentiation to neurons and increased the number of converted neuronal cells to 14.17% – the highest efficiency of neuronal transformation achieved to date using non-viral gene delivery. The converted cells had functional characteristics of mature neurons as evidenced by the presence of neuronal markers and electrophysiological activity.

Triboelectric stimulation for direct conversion of fibroblasts into neurons. Contact between the plates induces surface friction (intensified by PDMS’s micro-pillar structure) and electron transfer from the Al layer (light blue) to the PDMS layer (dark blue) (i). In the releasing state, negative charges on the PDMS layer generate positive charges in the Cu electrode (yellow), creating difference in electric potential between the two plates (ii) and inducing current through cell culture substrate made of conductive titanium film deposited on the silicon surface (middle panel). The current continues until a sufficient distance is reached between the plates (iii); then, the top plate is pressed again and electrons flow in the opposite direction (iv). Thus, the triboelectric nanogenerator can produce biphasic electricity.

Success in a mammalian model
How can triboelectricity enhance the fibroblast-to-neuron transformation? To answer this question, the researchers performed confocal microscopy and protein expression analysis and found that electrical stimulation induced influx of Ca2+ ions, which activated intracellular signaling proteins triggering neuronal differentiation.

However, the results obtained in cell cultures may not necessarily be representative of the situation in an organism. Therefore, the scientists tested their triboelectric nanogenerator in mice who received intradermal injections of polymeric nanoparticles carrying neuronal transcription factors. Triboelectic current generated by the nanostimulator connected to the mouse skin increased the conversion of dermal fibroblasts into neuronal cells by over 100 times, proving that it is a powerful inducer of transformation from somatic cells to neurons in vivo.

Conclusions
Thus, the novel strategy based on triboelectric energy harvesting represents a less invasive non-viral method for rapid and efficient reprogramming of somatic cells into mature functional neurons, laying out a new direction for addressing challenges in the treatment of neurodegenerative diseases, stroke, and age-related neuronal loss. As the next step, the team of Professor Cho plans to develop a triboelectric nanostimulator that can collect energy from such body activities as breathing and cardiac pulses. The hope is that these portable self-powered nanoelectronic devices harnessing renewable energy sources such as human motions might one day be used for individual regulation of brain activity.